Cloning and analysis of a FoxO transcription factor from Xiphophorus
Melanoma development in the fish Xiphophorus is determined, at least in part, by overexpression and activation of the Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2...
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Veröffentlicht in: | Gene 2003-01, Vol.302 (1), p.31-41 |
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creator | Rudd, Michael D. Johnston, Dennis A. Kazianis, Steven Butler, Andrew P. |
description | Melanoma development in the fish
Xiphophorus is determined, at least in part, by overexpression and activation of the
Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2 with regulation of cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO sub-family) homolog from
Xiphophorus
maculatus. The isolated clone is a 2.7 kb cDNA encoding a predicted protein of 664 amino acids. The gene, which we have named
FoxO5, maps to
Xiphophorus Linkage Group XV. The protein product can be categorized within a branch of the FOXO sub-class, which includes:
Danio
rerio zFKHR (foxo5),
Homo
sapiens FKHR-L1 (FoxO3a) and
Mus
musculus FKHR2 (Foxo3). Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation sites and a carboxy-terminal minimal activation domain are each highly conserved. A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits proliferation, but the wild-type protein fails to do so, when exogenously expressed in
Xiphophorus cells derived from a melanoma. The same mutated protein predominantly localizes to the nucleus, yet the wild-type protein seldom does. Further characterization of
Xiphophorus FoxO5 will contribute to understanding the molecular basis of carcinogenesis in these species. |
doi_str_mv | 10.1016/S0378-1119(02)01100-9 |
format | Article |
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Xiphophorus is determined, at least in part, by overexpression and activation of the
Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2 with regulation of cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO sub-family) homolog from
Xiphophorus
maculatus. The isolated clone is a 2.7 kb cDNA encoding a predicted protein of 664 amino acids. The gene, which we have named
FoxO5, maps to
Xiphophorus Linkage Group XV. The protein product can be categorized within a branch of the FOXO sub-class, which includes:
Danio
rerio zFKHR (foxo5),
Homo
sapiens FKHR-L1 (FoxO3a) and
Mus
musculus FKHR2 (Foxo3). Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation sites and a carboxy-terminal minimal activation domain are each highly conserved. A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits proliferation, but the wild-type protein fails to do so, when exogenously expressed in
Xiphophorus cells derived from a melanoma. The same mutated protein predominantly localizes to the nucleus, yet the wild-type protein seldom does. Further characterization of
Xiphophorus FoxO5 will contribute to understanding the molecular basis of carcinogenesis in these species.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/S0378-1119(02)01100-9</identifier><identifier>PMID: 12527194</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animal model ; Animals ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; Cyprinodontiformes - genetics ; Cytoplasm - metabolism ; DNA, Complementary - chemistry ; DNA, Complementary - genetics ; DNA, Complementary - isolation & purification ; Female ; Forkhead ; FoxO5 ; FoxO5 gene ; Freshwater ; Gene Expression ; Genetic map ; Green Fluorescent Proteins ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Male ; Molecular Sequence Data ; Phylogeny ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Transcription Factors - genetics ; Tumor Cells, Cultured ; Xiphophorus maculatus ; Xmrk-2 gene</subject><ispartof>Gene, 2003-01, Vol.302 (1), p.31-41</ispartof><rights>2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-e7d106cee07a22ec82f854f39a3037dc461f03873934e1c08d9f410f0a2e3d583</citedby><cites>FETCH-LOGICAL-c392t-e7d106cee07a22ec82f854f39a3037dc461f03873934e1c08d9f410f0a2e3d583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378111902011009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12527194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rudd, Michael D.</creatorcontrib><creatorcontrib>Johnston, Dennis A.</creatorcontrib><creatorcontrib>Kazianis, Steven</creatorcontrib><creatorcontrib>Butler, Andrew P.</creatorcontrib><title>Cloning and analysis of a FoxO transcription factor from Xiphophorus</title><title>Gene</title><addtitle>Gene</addtitle><description>Melanoma development in the fish
Xiphophorus is determined, at least in part, by overexpression and activation of the
Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2 with regulation of cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO sub-family) homolog from
Xiphophorus
maculatus. The isolated clone is a 2.7 kb cDNA encoding a predicted protein of 664 amino acids. The gene, which we have named
FoxO5, maps to
Xiphophorus Linkage Group XV. The protein product can be categorized within a branch of the FOXO sub-class, which includes:
Danio
rerio zFKHR (foxo5),
Homo
sapiens FKHR-L1 (FoxO3a) and
Mus
musculus FKHR2 (Foxo3). Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation sites and a carboxy-terminal minimal activation domain are each highly conserved. A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits proliferation, but the wild-type protein fails to do so, when exogenously expressed in
Xiphophorus cells derived from a melanoma. The same mutated protein predominantly localizes to the nucleus, yet the wild-type protein seldom does. Further characterization of
Xiphophorus FoxO5 will contribute to understanding the molecular basis of carcinogenesis in these species.</description><subject>Animal model</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Chromosome Mapping</subject><subject>Cloning, Molecular</subject><subject>Cyprinodontiformes - genetics</subject><subject>Cytoplasm - metabolism</subject><subject>DNA, Complementary - chemistry</subject><subject>DNA, Complementary - genetics</subject><subject>DNA, Complementary - isolation & purification</subject><subject>Female</subject><subject>Forkhead</subject><subject>FoxO5</subject><subject>FoxO5 gene</subject><subject>Freshwater</subject><subject>Gene Expression</subject><subject>Genetic map</subject><subject>Green Fluorescent Proteins</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Phylogeny</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Homology, Amino Acid</subject><subject>Transcription Factors - genetics</subject><subject>Tumor Cells, Cultured</subject><subject>Xiphophorus maculatus</subject><subject>Xmrk-2 gene</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LAzEQQIMoWqs_QdmT6GF1Jtntbk4i1apQ8KCCtxCzE41sNzXZiv57Y1v06DBDLm8-8hg7QDhFwNHZPYiqzhFRHgM_AUSAXG6wAdaVzAFEvckGv8gO243xDVKUJd9mO8hLXqEsBuxy3PrOdS-Z7ppUuv2KLmbeZjqb-M-7rA-6iya4ee98l1lteh8yG_wse3LzV58yLOIe27K6jbS_fofscXL1ML7Jp3fXt-OLaW6E5H1OVYMwMkRQac7J1NzWZWGF1CJd2phihDYdXgkpCkIDdSNtgWBBcxJNWYshO1rNnQf_vqDYq5mLhtpWd-QXUWE9KmUpMIHlCjTBxxjIqnlwMx2-FIL60aeW-tSPGwVcLfUpmfoO1wsWzzNq_rrWvhJwvgIoffPDUVDROOoMNS6Q6VXj3T8rvgHksX5k</recordid><startdate>20030102</startdate><enddate>20030102</enddate><creator>Rudd, Michael D.</creator><creator>Johnston, Dennis A.</creator><creator>Kazianis, Steven</creator><creator>Butler, Andrew P.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>F1W</scope><scope>FR3</scope><scope>H95</scope><scope>H99</scope><scope>L.F</scope><scope>L.G</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20030102</creationdate><title>Cloning and analysis of a FoxO transcription factor from Xiphophorus</title><author>Rudd, Michael D. ; Johnston, Dennis A. ; Kazianis, Steven ; Butler, Andrew P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-e7d106cee07a22ec82f854f39a3037dc461f03873934e1c08d9f410f0a2e3d583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animal model</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Chromosome Mapping</topic><topic>Cloning, Molecular</topic><topic>Cyprinodontiformes - genetics</topic><topic>Cytoplasm - metabolism</topic><topic>DNA, Complementary - chemistry</topic><topic>DNA, Complementary - genetics</topic><topic>DNA, Complementary - isolation & purification</topic><topic>Female</topic><topic>Forkhead</topic><topic>FoxO5</topic><topic>FoxO5 gene</topic><topic>Freshwater</topic><topic>Gene Expression</topic><topic>Genetic map</topic><topic>Green Fluorescent Proteins</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Phylogeny</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Homology, Amino Acid</topic><topic>Transcription Factors - genetics</topic><topic>Tumor Cells, Cultured</topic><topic>Xiphophorus maculatus</topic><topic>Xmrk-2 gene</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rudd, Michael D.</creatorcontrib><creatorcontrib>Johnston, Dennis A.</creatorcontrib><creatorcontrib>Kazianis, Steven</creatorcontrib><creatorcontrib>Butler, Andrew P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>ASFA: Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rudd, Michael D.</au><au>Johnston, Dennis A.</au><au>Kazianis, Steven</au><au>Butler, Andrew P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cloning and analysis of a FoxO transcription factor from Xiphophorus</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2003-01-02</date><risdate>2003</risdate><volume>302</volume><issue>1</issue><spage>31</spage><epage>41</epage><pages>31-41</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>Melanoma development in the fish
Xiphophorus is determined, at least in part, by overexpression and activation of the
Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2 with regulation of cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO sub-family) homolog from
Xiphophorus
maculatus. The isolated clone is a 2.7 kb cDNA encoding a predicted protein of 664 amino acids. The gene, which we have named
FoxO5, maps to
Xiphophorus Linkage Group XV. The protein product can be categorized within a branch of the FOXO sub-class, which includes:
Danio
rerio zFKHR (foxo5),
Homo
sapiens FKHR-L1 (FoxO3a) and
Mus
musculus FKHR2 (Foxo3). Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation sites and a carboxy-terminal minimal activation domain are each highly conserved. A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits proliferation, but the wild-type protein fails to do so, when exogenously expressed in
Xiphophorus cells derived from a melanoma. The same mutated protein predominantly localizes to the nucleus, yet the wild-type protein seldom does. Further characterization of
Xiphophorus FoxO5 will contribute to understanding the molecular basis of carcinogenesis in these species.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>12527194</pmid><doi>10.1016/S0378-1119(02)01100-9</doi><tpages>11</tpages></addata></record> |
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subjects | Animal model Animals Base Sequence Chromosome Mapping Cloning, Molecular Cyprinodontiformes - genetics Cytoplasm - metabolism DNA, Complementary - chemistry DNA, Complementary - genetics DNA, Complementary - isolation & purification Female Forkhead FoxO5 FoxO5 gene Freshwater Gene Expression Genetic map Green Fluorescent Proteins Luminescent Proteins - genetics Luminescent Proteins - metabolism Male Molecular Sequence Data Phylogeny Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Sequence Analysis, DNA Sequence Homology, Amino Acid Transcription Factors - genetics Tumor Cells, Cultured Xiphophorus maculatus Xmrk-2 gene |
title | Cloning and analysis of a FoxO transcription factor from Xiphophorus |
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